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Controversies Withthe Diagnosis andManagement of

HELLP SyndromeJOHN M. OBRIEN, MD and JOHN R. BARTON, MD

Perinatal Diagnostic Center, Central Baptist Hospital,Lexington, Kentucky

IntroductionThe spectrum of disease resulting from the

pathophysiology of preeclampsia continuesto challenge the diagnostic acumen of clini-

cians. One of preeclampsias various mani-festations includes the specific entity ofHELLP syndrome. Recently, investigatorshave provided evidence some cases ofHELLP syndrome represent a vasculopathymediated by an abnormal concentration ofvascular growth factors.1 However, untilthe underlying etiology for preeclampsia is

better defined and testing for such factorsis commonplace, controversies in the diag-nosis and management of HELLP syndromewill persist as its numerous clinical findingswill lead to varied inpressions of severityand to varied thresholds for intervention.

Controversies in DiagnosisThe preeclamptic patient with the constella-tion of hemolysis, hepatic dysfunction, and

low platelets has been described in the liter-ature for decades with early accurate descrip-tions by Prichard et al and Chesley.2,3 It wasnot until 1982, however, when Weinstein

coined the acronym HELLP syndrome (he-molysis, elevated liver enzymes, and low

platelets) that clinicians could more easilyrecognize and discuss this group of patientswith remarkable hepatic involvement bysevere preeclampsia.4

Investigations into the pathophysiologyof preeclampsia, and specifically HELLPsyndrome, have revealed a disorder charac-terized by hepatic endothelial disruptionfollowed by platelet activation, aggregation,and consumption ultimately resulting in dis-tal ischemia and hepatocyte death.5,6 Thisvasculopathy can be limited to a hepaticsegment or occur diffusely throughout theliver. Most commonly, HELLP syndromeinvolves smaller terminal arterioles yieldinga process with characteristic histologic fea-tures. The classic hepatic lesion associa-ted with HELLP syndrome is periportal orfocal parenchymal necrosis in which hyalinedeposits of fibrin-like material can be seen

Correspondence: John M. OBrien, MD, Director, PerinatalDiagnostic Center, Central Baptist Hospital, 1740 Nicholas-villeRoad, Lexington,KY 40503.E-mail:[email protected]

CLINICAL OBSTETRICS AND GYNECOLOGY / VOLUME 48 / NUMBER 2 / JUNE 2005

CLINICAL OBSTETRICS AND GYNECOLOGYVolume 48, Number 2, 460477 2005, Lippincott Williams & Wilkins

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in the sinusoids.79 Alternatively and lessfrequently, larger-vessel disease can impactwider vascular distributions in the liver withmore catastrophic outcomes such as hepaticinfarction or subcapsular hematoma. Thisrare large-vessel disease is more readily vis-ible by imaging studies such as magneticresonance imaging (MRI) or computed to-mography (CT) scanning and is associatedwith worse laboratory values indicating moredramatic hepatic dysfunction.10

The greatest controversy involving HELLP

syndrome is in the diagnosis of the condi-tion. The syndrome outlined by Weinsteinin the early 1980s provided a descriptionof the disease process and gave cliniciansan easier framework to understand the path-ophysiology. Namely, his group of 29 pa-tients with severe preeclampsia/eclampsiamanifested more pronounced hepatic in-volvement rather than primarily cerebral orrenal disease. Later, Sibai et al establishedlaboratory criteria for the diagnosis and pro-vided standards for subsequent discussionsin the literature (see Table 1).11 In his clas-

sification, Sibai defined laboratory abnor-malities sufficient for the diagnosis of eachelement of the syndrome: hemolysis by anabnormal peripheral smear, elevated biliru-

bin .1.2 mg/dL, or elevated lactate dehy-drogenase (LDH) .600 U/L; elevated liverenzymes by an aspartate aminotransferase(AST) .70 IU/L (which was greater than2 standard deviations of normal) and lactatedehydrogenase (LDH) .600 U/L; and low

platelets defined as 100,000/mm3, as this valuewas standard in other fields of medicine.

Martin et al also attempted to classify thedisease noting an increase in untoward out-comes, including cardiopulmonary, centralnervous system, and renal dysfunction, asthe degree of thrombocytopenia worsened.12

In their retrospective review of 302 casesof HELLP syndrome, they defined class 1HELLP syndrome as a platelet nadir below50,000/mm3, whereas those with platelet na-dirs between 51,000 and 100,000/mm3 weredefined as class 2. Class 3 HELLP syn-drome represented a newly classified group

of patients with hepatocyte death buta higher platelet count nadir, 101,000 to150,000/mm3. In this series, thrombocyto-

penia in women with HELLP syndromewas found to represent a marker for moreextensive endothelial disruption and hepato-cyte death as peak aminotransferase valuescorrelated well with platelet nadirs. Stillothers have offered differing criteria forthe diagnosis of HELLP syndrome to Sibaisand Martins, each assessing varyingdegrees of hepatic involvement as evidenced

by liver function test abnormalities to repre-

sent thresholds for diagnosis (see Table1).13,14 Despite the best of intentions, thesediffering depictions of HELLP syndromewith differing criteria for platelet countand liver function test abnormalities havecreated a rationale for questioning findingsof individual reports and have likely con-fused clinicians.

Compared with the 1980s, when Weinsteinfirst coined the term, HELLP syndrome andits variants are now more commonly recog-nized earlier when platelet consumption yields

TABLE 1. Classifications of HELLP Syndrome

Platelet Count AST LDH

Sibai et al11 ,100,000/mm3 $70 U/L $600 U/LMartin et al12 ,150,000/mm3 $40 U/L $600 U/Lvan Pampus13 ,100,000/mm3 .50 U/L .600 U/LVisser and Wallenburg14 ,100,000/mm3 .30 U/L *

* Not included in their criteria.

Reprinted from Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. 2004;103:981991.

AST, aspartate aminotransferase; LDH, lactic dehydrogenase.

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milder degrees of thrombocytopenia and ele-vated liver function tests document hepaticischemia. It appears, however, the same path-ophysiology is ongoing whether the patienthas evidence of thrombocytopenia and elevatedliver function tests alone or whether schisto-cytes are present in the peripheral smear, theserum bilirubin is elevated, or other abnor-malities such as coagulopathy or renal insuf-ficiency have unfolded. With greater involve-ment of the endothelium of the liver by

preeclampsia, more red blood cells are he-

molyzed and more hepatic ischemia re-sults with the combination yielding higher

bilirubin levels and impaired coagulationstudies.

Thus, the primary controversy in the di-agnosis of HELLP syndrome has been in

precisely defining when in the spectrumof the hepatic involvement with preeclamp-sia does the true HELLP syndrome de-velop. Some patients have been termed ashaving partial HELLP syndrome, ELLPsyndrome, or class 3 HELLP syndrome.These women are also at risk for signif-

icant maternal and fetal morbidity as aresult of this same pathophysiology despitecriticisms that elements of the true dis-ease may be missing. In a study by VanPampus et al, 10% of women with ELLPsyndrome were identified as having seriouscomplications, including eclampsia, cerebralischemia, and abruptio placentae comparedwith a 24% rate for women with trueHELLP.13 In a study by Abramovici et al,the rate of fetal distress (13% vs. 18%) andintrauterine growth restriction (28% vs.31%) was lower in women with HELLP syn-drome versus the partial HELLP group.15

These data do not demonstrate that a suffi-ciently different outcome occurs in patientswith hepatic involvement by preeclampsiato justify subdividing these patients intominute subclassifications. Unfortunately, itappears once severe preeclampsia has man-ifested remarkable end-organ involvement,adverse renal, central nervous system, and

pulmonary complications can arise and should be anticipated.

For diagnostic criteria to be most useful,they should be based on objective criteria,testing should be readily available, and theresults of these tests should not be subjectto interpretation. These criteria should alsoattempt to identify earlier stages of the dis-ease process rather than limiting the diagno-sis to a small subset of only the most severecases. Finally, the definitions should be easyto use for the clinician.

The diagnosis of HELLP syndrome ismade by laboratory parameters alone, al-

though supporting typical findings of pre-eclampsia, including hypertension and pro-teinuria, help rule out other potential imita-tors (see the next section on differentialdiagnosis). Laboratory evaluation should in-clude a complete blood count with plateletcount, a peripheral smear, coagulation stud-ies, serum AST, creatinine, glucose, biliru-

bin, and LDH levels. Ideally, the laboratoryparameters for HELLP syndrome should beintuitive,easytoremember,andconsistentbe-tween laboratories. Of the laboratory studiesroutinely obtained for diagnostic purposes,

platelet count and liver function tests arethe best standardized and can fulfill thesecriteria.

The platelet count historically used to di-agnose thrombocytopenia is ,100,000/mm3

and is the threshold most consistent acrossall specialties of medicine. The liver func-tion tests profile we use is that presented

by Sibai as AST or ALT. 2 times the upperlimit of normal or 70 U/L. To assess thedegree of hemolysis, we do not evaluate

peripheral smears ourselves or ask hematol-ogists/pathologists to provide middle-of-the-night evaluations. We do use an LDH valueto give an indication for hemolysis as sug-gested by Sibai. We are also cognizant, how-ever, that an elevated LDH, most of the time,also reflects hepatocyte destruction in addi-tion to hemolysis. Therefore, in our opinion,a complete blood count and metabolic pro-file are readily available, rapidly performedtests, which allow recognition and definitionof severe involvement of liver parenchyma

by preeclampsia. The alphabet soup present

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in the literature attempting to differentiateHELLP versus ELLP versus EL versusHEL syndrome, or partial HELLP versusHELLP, is of limited value when attemptingto treat a patient identified with significant he-

patic involvement from severe preeclampsia.We anticipate that expert groups focused onthe care for women with hypertensive disor-ders in pregnancy can better define the clinicalcondition of hepatic involvement by pre-eclampsia and eliminate the current confusionand controversy.

Differential DiagnosisSibai has noted that most patients withHELLP syndrome present preterm withhypertension, and proteinuria, and reportepigastric or right upper quadrant pain.16

Unfortunately, however, other patients pres-ent with only nausea or vomiting, and stillothers may have nonspecific viral-likesymptoms. In Weinsteins second report,17

nausea or vomiting and epigastric pain werethe most common symptoms. A pregnantwoman in the late second or early thirdtrimester with right upper quadrant pain,epigastric pain, or identified hepatic dys-function should be considered as havingHELLP syndrome until other elements ofthe differential diagnosis are excluded (seeTable 2). Epigastric pain may antedate the

laboratory abnormalities of HELLP syn-drome by several hours, leading cliniciansto question initial impressions. Symptomsof upper quadrant pain without laboratoryabnormalities may lead errantly to diagnosesof gastritis or gallbladder disease. Reevalu-ation of laboratory studies in 4 to 6 hoursafter onset of symptoms usually confirmsan initial clinical suspicion of HELLPsyndrome.

Patients with HELLP syndrome frequentlydemonstrate significant weight gain with

generalized edema. However, severe hyper-tension (systolic blood pressure$160 mm Hg,diastolic blood pressure $110 mm Hg) isnot a constant finding in HELLP syndrome.Although 69% of the 112 patients studied bySibai et al had a diastolic blood pressure$110 mm Hg at admission to the hospital,15% had a diastolic blood pressure of#90 mm Hg. In Weinsteins5 initial report,less than half (13) had an admission blood

pressure$160/110 mm Hg. Thus, hyperten-sion is not obligatory to diagnose HELLPsyndrome. More significant renal involve-

ment by preeclampsia compared with hepaticdisease appears better correlated with the se-verity of hypertension.

Once laboratory abnormalities sufficientto diagnose HELLP syndrome are observed,other hepatopathies may be considered andeliminated as possibilities. Concomitant hy-

poglycemia, coagulopathy, elevated ammo-nia level, and renal dysfunction are associatedwith acute fatty liver of pregnancy. Cerebraldysfunction, fever, and rash may be part ofthrombotic thrombocytopenic purpura. He-molytic uremic syndrome is primarily a renaldisease in children and is related to infectionwith Escherichia coli. In adults, almost allcases develop in the postpartum period. Exac-erbation of systemic lupus erythematosus withnephritis can also mimic severe preeclampsia.The clinical manifestations and laboratoryfindings of the various conditions presentedin Table 2 can be differentiated from severe

preeclampsia. Occasionally, however, the timecourse of the condition and prompt postpar-tum resolution of laboratory studies are the

TABLE 2. Medical and Surgical Disorders Potentially ConfusedWith HELLP Syndrome

Acute fatty liveror pregnancy

Hyperemesis gravidarumIdiopathic thrombocytopenia

AppendicitisCholestasis of

pregnancy

Kidney stonesPeptic ulcerPyelonephritis

Diabetes insipidus Systemic lupus erythematosusGallbladder diseaseGastroenteritis

Thromboticthrombocytopenic purpura

Glomerulonephritis Viral hepatitisHemolytic uremic

syndromeHepatic

encephalopathy



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only means to determine the etiology for ma-ternal disease.

Finally, clinicians should be familiar withthe various endothelial vascular organs thatcan be affected by preeclampsia. Althoughinvolvement in the renal and hepatic vesselsis most common, other vessels potentiallyaffected include the cerebral, cardiac, and

pulmonary. Involvement by this vasculop-athy of these organs can yield concomitanteclampsia, myocardial dysfunction, and pul-monary edema, and acute respiratory dis-

tress syndrome, adding to the diagnosticchallenges.

Management ControversiesThe diagnosis of HELLP syndrome has long

been recognized as heralding the need foraggressive, standardized therapies, includ-ing magnesium sulfate administration, anti-hypertensive therapy, and delivery to reduceassociated maternal morbidity and mortality(see Table 3).18 Several critical steps are in-volved in the management of these casesand are summarized in Figure 1. This check-

list for the management of the condition pro-vides an orderly sequential approach.

The clinical course of women withHELLP syndrome is usually characterized

by progressive and sometimes sudden dete-rioration in maternal and fetal conditions.Therefore, patients with suspected diagnosisof HELLP syndrome should be hospitalizedimmediately and observed in a labor and de-livery unit. The first priority is to assess andstabilize the maternal condition, particularlycoagulation abnormalities. Patients with

HELLP syndrome who are remote fromterm should be referred to a tertiary carecenter.

Such patients should be managed as hav-ing severe preeclampsia and should initiallyreceive intravenous (IV) magnesium sulfateas prophylaxis against seizures and antihy-

pertensive medications to keep systolicblood pressure below 160 mm Hg and/or di-astolic blood pressure below 105 mm Hg.19

This can be achieved with a 5-mg bolus doseof hydralazine, to be repeated as neededevery 15 to 20 minutes for a maximum dose

of 20 mg per hour. Blood pressure is recordedevery 15 minutes during therapy and everyhour once the desired values are achieved.If hydralazine does not lower blood pressureadequately and/or if maternal side effectssuch as tachycardia or headaches develop,another drug such as labetalol or nifedipinecan be used. The recommended dose oflabetalol is 20 to 40 mg IV every 10 to 15minutes for a maximum of 220 mg over1 hour, and the dose of nifedipine is 10 to20 mg orally every 30 minutes for a maxi-mum dose of 50 mg over 1 hour. During theobservation period, maternal and fetal con-ditions are assessed.

The recommended regimen of magne-sium sulfate is a loading dose of 6 g givenover 20 minutes followed by a maintenancedose of 2 g per hour as a continuous IV so-lution. Magnesium sulfate is initiated at the

beginning of the observation period andthen continued during labor and for at least24 hours postpartum. The next step is toevaluate fetal well-being using the nonstress

TABLE 3. Serious Maternal Complicationsin 442 Patients With HELLP Syndrome

Complication No. Percent

Disseminated intravascularcoagulopathy 92 21

Abruptio placentae 69 16Acute renal failure 33 8Severe ascites 32 8

Pulmonary edema 26 6Pleural effusions 26 6Cerebral edema 4 1Retinal detachment 4 1Laryngeal edema 4 1Subcapsular liver

hematoma 4 1Acute respiratory distress

syndrome 3 1Death, maternal 4 1

Reprinted from Sibai BM. Diagnosis and management of gesta-tional hypertension and preeclampsia. Obstet Gynecol. 2003;102:181192.



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test or biophysical profile, as well as to ob-tain ultrasonographic biometry for assess-ment of possible intrauterine growth retarda-tion. Finally, a decision must be made as towhether immediate delivery is indicated.

Steroids and the Managementof HELLP SyndromeSeveral retrospective studies have demon-strated glucocorticoids can also impact the

maternal condition in patients with HELLPsyndrome, thereby adding another newerintervention to this armementarium.2024

Five randomized trials comparing the useof high-dose dexamethasone with either notreatment21,22,25,26 or with betamethasone27

in women with presumed HELLP syndromewere summarized by Sibai28 and are pre-sented in Table 4. The results of these stud-ies demonstrate improved laboratory valuesand urine output in patients receiving

FIGURE 1. Checklist in the management of HELLP syndrome.



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dexamethasone, but provide limited evi-dence of reduced maternal morbidity. How-ever, because most of these trials were

performed postpartum, the true extentglucocorticoids can influence outcomes

has yet to be determined.The mechanism of action of this drug is

unknown but appears to alter the final stepsin endothelial cell disruption as evidenced

by steroids having the ability to improve lab-oratory values postpartum when presumablythe ability to synthesize new mediators ofdisease is limited after delivery of the pla-centa. Because HELLP syndrome is charac-terized by the endothelial damage within theliver, we can only surmise glucocorticoidsact to minimize the degree of intravascularendothelial injury within the body, improve

blood flow within the liver specifically, andhalt ongoing hepatocyte death and plateletconsumption.

Because glucocorticoids are the only knowndrugs to improve the maternal laboratoryfindings in cases of severe preeclampsia, weuse this observation in our management.Our dosing of the medication is directednot only to improve neonatal outcomes bylowering the incidence of such complica-tions as respiratory distress syndrome and

intraventricular hemorrhage, but also to at-tempt to reduce maternal morbidity. Thedose, route of administration, and durationof treatment of glucocorticoids is importantand has varied between studies. These

aspects of therapy still require further studywith properly controlled trials, but some in-formation is evident from the literature.First, intravenous glucocorticoids appearto have a more rapid onset of action com-

pared with intramuscular dosing. The ran-domized trial by Isler et al demonstrated in-travenous dosing was superior to intramus-cular dosing for several outcome variables,including improving urine output and greaterimprovement in laboratory values.27 Sec-ond, glucocorticoids improve the maternalcondition in a dose-dependent manner.In a review of data collected at our center,we observed maternal platelet count in-creased more dramatically before deliverywith a high-dose protocol of glucocorticoidsversus standard regimens used for enhanc-ing lung maturity.24 We therefore use thishigh-dose protocol in our management of

patients with severe maternal disease (seeTable 5). Finally, the duration of action ofthis medication is limited and patients mayexperience a worsening of their laboratory

TABLE 4. Randomized Trials of Corticosteroids In Women With ELLP Or HELLP Syndrome

AuthorsDexamethasone(no.)

Control(no.) Key Finding

Magann et al21 12* 13 Improved platelet, ALT, LDH values indexamethasone group

Magann et al22 20 20 Improved platelet, AST, LDH, urine output,MAP in dexamethasone group

Vigil-De Gracia25 17 17 Improved platelet counts only with dexamethasoneYalcin et al26 15 15 Improved platelet, AST, MAP, and urine output

with dexamethasoneIsler et al27 19* 21 Improved AST, LDH, MAP, and urine output

with dexamethasone

* Antepartum. Postpartum.

Received intramuscular betamethasone.

Reprinted from Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. 2004;103:981991.

ELLP, elevated liver enzymes and low platelets; AST, aspartate amino transferase; ALT, alanine amino transferase; LDH, lactic dehy-drogenase; MAP, mean arterial pressure.



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studies 48 to 72 hours after dosing with glu-cocorticoids.23,24 We term this finding therebound phenomenon. Steroid treatment,therefore, is not curative but may createa window of opportunity for intervention

before the maternal condition may againdeteriorate.

During the period when the maternal sta-tus is being optimized, adequate but notexcessive hydration of the patient is per-

formed, laboratory studies are followed toobserve the expected response, and the fetalstatus is intermittently reassessed. Becauseglucocorticoids do not appear to alter theunderlying pathophysiology, delivery re-mains the only definitive therapy. We do not

proceed with expectant management ofHELLP syndrome beyond an appropriate in-terval to optimize the maternal status andobtain fetal exposure to the drug (2448hours). Furthermore, if no improvement inthe clinical or laboratory status is notedwithin 8 to 12 hours of administration ofthe medication, we reevaluate the diagnosisconsidering other conditions such as acutefatty liver, consider increasing the dose ofglucocorticoid, consider transfusion, and ex-

pedite delivery.With this information, we have created

flowsheets for the management of antepar-tum and postpartum HELLP syndrome(see Figs. 2A and B). Understanding thegoals of therapy are essential to optimal out-comes and are 2-fold: 1) to improve the ma-

ternal status immediately before and duringdelivery if needed, and 2) in women ,35weeks, to provide glucocorticoid exposureto the fetus for enhancement of fetal lungmaturation.

We believe that glucocorticoids may beused for maternal benefit even if the patienthas previously received this medication forfetal lung maturity in the current pregnancy.We therefore attempt to delineate mater-nal versus fetal indications for the use ofglucocorticoids in patients with HELLP

syndrome.An increase in maternal platelet count be-

fore delivery can alter management bypotentially minimizing bleeding complica-tions. For instance, with treatment, we haveobserved a significant increase in the use ofregional anesthesia in those women withHELLP syndrome exposed to glucocorti-coids for 24 hours compared with womenwho did not receive this therapy or achievethis latency period.29 We therefore coordi-nate our efforts with our anesthesiologists

before effecting delivery, attempting to max-

imize the maternal platelet count and thereby increase the use of regional anesthesia.Regional anesthesia has been shown toavoid complications of exacerbated hyper-tension, aspiration, and failed intubationattributable to general anesthesia in this pop-ulation. We have given glucocorticoids atany gestational age to address maternal dis-ease because such a benefit may exist interm gestations. However, the use of high-dose dexamethasone to improve maternaloutcome in women with HELLP syndrome

beyond 34 weeks gestation and/or in the postpartum period remains experimental.

A latency period before effecting deliveryis not appropriate or necessary in all casesof HELLP syndrome but is required to expecta benefit from glucocorticoid administration.If the gestational age is$35 weeks, the patientis asymptomatic, and the platelet count is suf-ficient to offer any type of anesthesia, we pro-ceed promptly with delivery and do not sug-gest a latency period for glucocorticoids toimpact the maternal status. Alternatively, the

TABLE 5. High-Dose GlucocorticoidTherpy to Improve Laboratory Abnormalities in Patients With HELLP Syndrome

For most patients with HELLP syndrome, 10 mgintravenous dexamethasone every 6 hours for 2doses followed by 6 mg intravenous dexamethasoneevery 6 hours for 2 additional doses.

For select patients at highest risk, including thosewith profound thrombocytopenia (,20,000/mm3)or with central nervous system dysfunction(ie, blindness, paralysis), 20 mg intravenousdexamethasone every 6 hours for up to 4 doses.



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fetal status may not allow for expectant man-agement and a sufficient latency period to op-timize both the fetal and maternal condition. Ifa nonreassuring fetal assessment is observed,we consider initiating our steroid protocolwhen the maternal disease is severe. We pro-ceed with delivery and expect the impact ofour therapy to begin postpartum.

Conservative ManagementProlonging the latency period beyond 48

hours from the time of the diagnosis ofHELLP syndrome to delivery is controver-sial. van Pampus et al described the clinical

progress and maternal outcome of theHELLP and ELLP (findings of HELLP syn-drome but without evidence of hemolysis)syndrome in 127 patients managed in theAcademic Medical Center in Amsterdam

between 1984 and 1996 with a live fetusin utero.13 The patients were treated by tem-

porizing management, including the use ofantihypertensives and magnesium sulfate.The predominant indication for terminating

pregnancy was fetal distress or fetal deathand not maternal condition. All serious ma-ternal complications occurred at the onset ofthe syndrome (24% of cases with HELLPsyndrome vs. 10% with ELLP). Two motherswith HELLP syndrome died after a cerebralhemorrhage. Seventy-nine (62%) of womenwere not delivered after 3 days and 65 (51%)after 7 days. Although the authors noted it isunlikely that a more aggressive approachwould have reduced maternal mortality ormorbidity, their sample size was inadequateto evaluate rare serious maternal complica-tions of HELLP or ELLP syndrome.

In a study by Visser and Wallenburg,14

128 consecutive preeclamptic patients withHELLP syndrome and a gestational age lessthan 34 weeks gestation were matched formaternal and gestational age with 128

preeclamptic patients without HELLP syn-drome. Both groups were treated with vol-ume expansion and pharmacologic vasodila-tation under invasive hemodynamic monitor-ing with the aim of prolonging gestation and

enhancing fetal maturity. Except for variables pertaining to HELLP syndrome, clinical andlaboratory data and median prolongation of

pregnancy did not differ between the groups.Perinatal mortality was 14.1% in patients withHELLP syndrome and 14.8% in patients with-out HELLP. Because the perinatal outcomesin this study are similar to studies performedin the United States where delivery was af-fected within 48 hours of the diagnosis ofHELLP syndrome, the benefit of temporizingmanagement of HELLP syndrome remains

questionable. Ultimately, only a well-designedrandomized trial will resolve this managementissue.

The described conservative managementtechniques were often associated with theuse of invasive procedures and numerousmedical and surgical treatments. These con-founding variables make it difficult to eval-uate any treatment modality proposed forthis syndrome. Occasionally, some patientswithout true HELLP syndrome may demon-strate antepartum reversal of hematologicabnormalities after bedrest, the use of ste-

roids, or plasma volume expansion. How-ever, in our experience, the majority of these

patients demonstrate progressive deteriora-tion in either maternal or fetal condition.The potential risks associated with conser-vative management of HELLP syndrome in-clude abruptio placentae, pulmonary edema,acute renal failure, eclampsia, perinatal death,and maternal death. Therefore, because onlya limited prolongation of pregnancy can

be expected and because no difference infetal survival with aggressive attempts atexpectant management has been observed,we caution against expectant management

beyond a 24- to 48-hour latency to optimizethe maternal status for delivery. We shouldspecifically caution women with dissemi-nated intravascular coagulation (DIC) shouldnot be expectantly managed.

TransfusionPlatelet transfusions are indicated either be-fore or after delivery in all patients with



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FIGURE 2. A, Flowchart for antepartum HELLP syndrome. B, Flow-chart for postpartum management of HELLP syndrome.



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HELLP syndrome in the presence of signif-icant bleeding from puncture sites, wound,intraperitoneal, extensive ecchymosis, andso on. Furthermore, transfusion is indicatedin all antepartum patients whose plateletcount is less than 20,000/mm3. Correctionof profound thrombocytopenia is particu-larly important before cesarean section. Re-

peated platelet transfusions, however, maynot be necessary because consumption occursrapidly and the effect is transient. Our policyis to administer 6 to 10 units of platelets in

all patients with a platelet count less than40,000/mm3 before intubating the patientfor cesarean section.

Platelets are the most commonly trans-fused blood component in patients withHELLP syndrome. However, red cells andfresh-frozen plasma may also be needed in

patients with more severe coagulopathies.The need for transfusion may be reduced

by optimizing the patients status before de-livery and reducing the severity of thrombo-cytopenia. Martin et al have demonstrateda reduction in the rate for transfusion of both

cellular components and plasma in patientsexposed to dexamethasone over 2 epochs.30

The association between dexamethasone ex-posure and a reduced rate of transfusion hasalso been noted by our group. The decisionto delay delivery to improve the maternal

platelet count by steroid exposure is againdependent on several aspects of the clinicalsituation, including fetal status. A large,multicenter, placebo-controlled, randomizedtrial of patients with markedly thrombocyto-

penic, antepartum HELLP syndrome wouldbe necessary to quantitate the potential ben-efit of reduced need for transfusion after ste-roid exposure. Such a trial does not appearto be forthcoming, however, especially whenconsidering the fetal benefits to glucocorti-coid administration for lowering the rateof complications of prematurity.

Delivery ControversiesDelivery of a patient with HELLP syndromeis associated with numerous potential com-

plications, including postpartum hemor-rhage, vaginal/labial hematoma for vaginaldelivery, wound hematomas/separation forcesarean delivery, and infection resultingfrom prolonged induction. The choice be-tween attempted vaginal delivery versuscesarean section should be based on assess-ment of various predictors for success of anattempted induction, including 1) cervicalstatus, 2) fetal heart rate tracing or biophys-ical profile, and 3) umbilical artery Dopplerstudies. We have observed a very poor suc-

cess rate for attempted induction in the faceof a preterm gestation with intrauterinegrowth restriction and markedly abnormalDoppler studies. We proceed directly tocesarean section under such circumstances.31

Briggs et al32 evaluated wound complica-tions between patients with antepartumHELLP syndrome with primary closure ver-sus delayed closure and Pfannenstiel versusmidline skin incisions. A total of 104 patientswere identified; 75 had a primary skin closureand 29 had a delayed closure 48 to 72 hours

postoperatively. Immediate wound complica-

tions (wound infection, hematoma) occurredin 18 (26%) patients who had primary closureversus 8 (24%) who had a delayed closure(odds ratio, 1.13; 95% confidence interval,0.393.27). A late wound breakdown wasseen in only 1 patient with primary closure

but in none with delayed closure. No statisti-cal difference in wound complication wasfound between midline (primary or delayed)and Pfannenstiel (primary, delayed) incisions(odds ratio, 0.65; 95% confidence interval,0.231.88). The authors concluded that forwomen with antepartum HELLP syndromedelivered by cesarean section, the frequencyof wound complications is not influenced bytype of skin incision or time of skin closure(primary or delayed).

Generalized oozing from any operativesite is very common in thrombocyto-

penic patients. To minimize the risk of he-matoma formation, the bladder flap should

be left open and a subfascial drain may beused for 24 to 48 hours. A subcutaneousdrain may also be considered if the skin is



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approximated attempting to minimize the in-cidence of wound complications. Subcutane-ous tissues should be approximated withsutures as evidenced by randomized trialsand metaanalysis for skin closure at cesareandelivery.33

Controversies in Managementof Subcapsular HematomaThe most dramatic sequelae of hepatic in-

volvement by preeclampsia is the develop-ment of segmental hepatic infarction, exten-sive parenchymal hemorrhage, or subcapsu-lar hematoma. Hepatic imaging findings inselected patients with HELLP syndromecan identify these abnormalities.10 Ruptureof a subcapsular hematoma is particularlyconcerning because it can lead to death byexsanguination from the inability to control

bleeding as a result of surgical difficultieswith repair of the liver and coagulopathy.Of the 34 patients evaluated by Bartonand Sibai, 16 patients (47%) had abnormal

hepatic imaging results. The most commonCT abnormalities were subcapsular hema-toma of the liver (n = 13) and intraparenchy-mal hemorrhage (n = 6).

Comparison of the clinical characteristicsand laboratory evaluations of patients withnormal and abnormal hepatic imaging find-ings demonstrated a significant difference in

platelet count nadir between the patientswith normal and abnormal imaging findings

but failed to show any statistically signifi-cant difference in gestational age, meanarterial pressure, or the other laboratory

parameters studied. Of the 13 patients withsevere thrombocytopenia (platelet count,20,000/mm3), 10 (77%) had abnormalhepatic imaging findings. Emergency inter-vention was needed for 6 patients on the ba-sis of these imaging findings. CT and MRIhave excellent sensitivity for detecting acuteliver hemorrhage, but because CT was moreavailable, faster, and safer for potentially un-stable patients, and hence was the imagingmodality of choice.

The differential diagnosis of an unrupturedsubcapsular hematoma of the liver in preg-nancy should include acute fatty liver of

pregnancy, abruptio placentae with dissemi-nated intravascular coagulation, ruptureduterus, or sepsis. Most patients with a subcap-sular hematoma of the liver are seen in thelate second or third trimester of pregnancy,although cases have been reported in the im-mediate postpartum period. Patients typicallyreport right upper quadrant pain, but local-ized pain may be absent. Stimulation of the

phrenic nerve at the diaphragm can producereferred pain along this nerves distribution toits origin in the C4C5 cervical plexus, in-cluding the pericardium, peritoneum, pleura,and shoulder. Physical examination findingsconsistent with peritoneal irritation and hepa-tomegaly may be present.

Surgical repair has been recommendedfor hepatic hemorrhage without liver rup-ture. More recent experience suggests, how-ever, this complication should be managedconservatively in patients who remainhemodynamically stable.34,35 Management

should include close monitoring of hemody-namics and coagulation status. Serial assess-ment of the subcapsular hematoma with ul-trasound or CT is necessary with immediateintervention for rupture or worsening of ma-ternal status. It is important with conserva-tive management to avoid exogenous sour-ces of trauma to the liver such as abdominal

palpation, convulsions, or emesis, and to usecare in transportation of the patient. Indeed,any sudden increase in intraabdominal pres-sure could potentially lead to rupture of thesubcapsular hematoma.36

In most instances, rupture of a subcapsularhematoma involves the right lobe and is pre-ceded by the development of a parenchymalhematoma. Patients frequently present withshoulder pain, shock, or evidence of massiveascites, respiratory difficulty, or pleural effu-sions, and often with a dead fetus. An ultra-sound or computed axial tomography of theliver should be performed to rule out the pres-ence of subcapsular hematoma of the liverand assess for the presence of intraperitoneal



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bleeding. Paracentesis confirms the presenceof intraperitoneal hemorrhage suspected byexamination or hepatic imaging.

The presence of ruptured subcapsular liverhematoma resulting in shock is a surgicalemergency requiring acute multidisciplinarytreatment. Resuscitation should consist ofmassive transfusions of blood, correction ofcoagulopathy with fresh-frozen plasma and

platelets, and immediate laparotomy. Optionsat laparotomy include packing and drainage(preferred), surgical ligation of the hemor-

rhaging hepatic segments, embolization ofthe hepatic artery to the involved liver seg-ment, and loosely suturing omentum or surgi-cal mesh to the liver to improve integrity. Evenwith appropriate treatment, maternal and fetalmortality is over 50%. Mortality is most com-monly associated with exsanguination andcoagulopathy. Initial survivors are at increasedrisk for developing adult respiratory distresssyndrome, pulmonary edema,37 and acute re-nal failure in the postoperative period.38

Smith et al39 reviewed their managementof 7 patients with spontaneous rupture of the

liver occurring during pregnancy. Of the 4survivors, the mean gestational age was32.8 weeks and the mean duration of hospi-talization was 16 days. All the survivorsmanaged with packing and drainage of theliver survived, whereas the 3 patients treatedwith hepatic lobectomy died. The authors al-so extracted 28 cases from the literaturereported since 1976. From a total of 35cases, 27 patients (82%) managed by pack-ing and drainage survived, whereas only25% of 8 patients undergoing hepatic lobec-tomy survived. The authors emphasized he-

patic hemorrhage with persistent hypoten-sion unresponsive to transfusion of blood

products may be managed surgically withlaparotomy, evacuation of the hematoma,

packing of the damaged liver, and drainingof the operative site. In certain cases inwhich the patient is stable enough to under-go angiography, transcatheter embolother-apy is a reasonable alternative to surgery.40

In a review of 442 cases of HELLP syn-drome managed at the University of Ten-

nessee, Memphis, 4 patients with HELLPsyndrome were complicated by a rupturedsubcapsular hematoma.18 Three cases re-quired transfusion of 22 to 40 units of

packed red blood cells and multiple unitsof platelets and fresh-frozen plasma. Twoof these 3 cases were complicated by pul-monary edema and acute renal failure, butall survived without any residual deficiency.The fourth case was a patient who presentedin profound shock and with disseminatedintravascular coagulopathy. This patient

subsequently died secondary to a ruptured pulmonary emphysematous bleb duringmanagement of adult respiratory distresssyndrome.

TABLE 6. Management of Patients With Subcapsular Hematoma of the Liver

General considerations:I. Have the blood bank aware of the potential

need for large amounts of packed red bloodcells, fresh-frozen plasma, and plateletconcentrate (ie, 30 units of blood, 20 units offresh-frozen plasma, 3050 units ofplatelets)

II. Consultation of a general or vascular surgeonIII. Avoid direct and indirect manipulation of the

liverIV. Close monitoring of hemodynamic statusV. Intravenous magnesium sulfate to prevent

seizuresIf the hematoma is unruptured:

I. Conservative management with serialcomputed tomography scans or ultrasound

If the hematoma is ruptured and patienthemodynamically unstable:I. Massive transfusions

II. Immediate laparotomyA. If bleeding is minimal:

1. Observation2. Draining area with closed suction

B. If bleeding is severe:1. Application of laparotomy sponges as

packsfor pressure

2. Embolization of the hepatic artery totheinvolved liver segment



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On the basis of review of the literature, anoutline for the management of hepatic com-

plications of HELLP syndrome was devel-oped (Table 6). This outline emphasizesthe potential for transfusion of large amountsof blood and blood products and the need foraggressive intervention if rupture of the he-matoma is suspected and the patient is he-modynamically unstable. We recommend30 units of packed red blood cells, 20 unitsof fresh-frozen plasma, 30 to 50 units of

platelets, and 20 to 30 units of cryoprecipi-

tate be available if rupture of a subcapsularhematoma is suspected. Our experience isin agreement with the recent observationsof Smith et al39 in that a stable patientwith an unruptured subcapsular hematomashould be conservatively managed. Constantmonitoring must continue during this man-agement, however, because patients canrapidly become unstable after rupture ofthe hematoma. Survival clearly is associatedwith rapid diagnosis and immediate medicalor surgical stabilization. Coagulopathy must

be aggressively managed. These patients

should be managed in an intensive care unitwith close monitoring of hemodynamic

parameters and fluid status to avoid pulmo-nary edema or respiratory compromise.

Postpartum ManagementThe diagnostic criteria for HELLP syndromemay develop antepartum or postpartum. Sibaiand associates18 revealed that 70% hadevidence of the syndrome antepartum, and30% developed the criteria postpartum. Inthe postpartum period, the time of onsetranged from a few hours to 7 days, withthe majority developing within 48 hours afterdelivery. Patients in this group are at in-creased risk for the development of pulmo-nary edema with acute renal failure.37,38

HELLP syndrome may be diagnosed post-partum following 1 of 3 clinical scenarios:1) worsening of antepartum severe pre-eclampsia with delivery not yet altering thetime course of the disease, 2) new onset ofsevere preeclampsia postpartum, or 3) re-

bound deterioration of a patient with antepar-tum HELLP syndrome after exposure to cor-ticosteroid antepartum.

The goals of therapy postpartum differcompared with antepartum and are aimedsolely at improving the maternal status.Management of seizure prophylaxis is sim-ilar to the antepartum patient with HELLPsyndrome, including the need for magne-sium sulfate. Hypertension control may bemore aggressive, however, because there isno longer concern about compromising the

uteroplacental circulation. Blood pressuregoals of systolic blood pressure,155 mm Hgand/or diastolic blood pressure,105 mm Hgare suggested.

After delivery, the patient should be mon-itored closely in an intensive care setting for24 to 48 hours. Most patients show evidenceof resolution of the disease process within48 hours after delivery. The differential diag-nosis of postpartum hypertension and pro-teinuria should include thrombotic throm-

bocytopenic purpura, hemolytic uremicsyndrome, and exacerbation of systemic lu-

pus. These alternative diagnoses may be con-sidered if resolution of the disease is pro-longed. However, some patients with HELLPsyndrome, especially those with DIC, maydemonstrate delayed resolution or even dete-rioration. Such patients may require longer,intensive monitoring. These patients are atrisk for developing pulmonary edema as aresult of transfusions of blood and blood

products, fluid mobilization, and compro-mised renal function.38

As a result of the persistent potential foradverse outcomes postpartum, severalreports have advocated the use of corticoste-roids to more promptly restore vascular in-tegrity. In a retrospective study, Martin et al41

reported the puerperal courses of 43 womenwith postpartum HELLP syndrome whowere treated with dexamethasone and com-

pared them with 237 similar patients whodid not receive corticosteroids. Dexametha-sone at a dosage of 10 mg IV at 12-hourintervals was given until disease remissionwas noted in treated patients, at which time



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up to 2 additional 5-mg IV doses were givenat 12-hour intervals. Patients who receiveddexamethasone for postpartum-onset HELLPsyndrome experienced a shorter diseasecourse, faster recovery, less morbidity, andless need for other interventionist therapycompared with a historical group of patientswith HELLP syndrome who did not receivedexamethasone.

Postpartum patients with delayed resolu-tion of HELLP syndrome (including persis-tent severe thrombocytopenia) represent

a management dilemma. Exchange plas-mapheresis with fresh-frozen plasma has

been advocated as a treatment by someauthors.4244 Because the majority of these

patients will have spontaneous resolutionof their disease, early initiation of plasma-

pheresis may result in unnecessary treat-ment. Schwartz44 suggested serial studiesindicating a progressive elevation of biliru-

bin or creatinine associated with hemolysisand thrombocytopenia may be an indicationfor plasmapheresis. Martin and coworkers42

reported the use of plasma exchange with

fresh-frozen plasma in 7 women in the post-partum period with HELLP syndrome thatpersisted .72 hours after delivery. All patients had persistent thrombocytopenia,rising lactic dehydrogenase, and evidenceof multiorgan dysfunction. The authors rec-ommended that a trial of plasma exchangewith fresh-frozen plasma be considered inHELLP syndrome that persists past 72 hoursfrom delivery and in which there is evidenceof a life-threatening microangiopathy.

Since their publication, however, the Mis-sissippi group has reviewed 18 patients withHELLP syndrome who were treated postpar-tum with single or multiple plasma ex-change with fresh-frozen plasma.43 Each pa-tient was entered into the clinical trial either

because of persistent evidence of atypical preeclampsiaeclampsia as HELLP syn-drome .72 hours after delivery (group 1)or with evidence of worsening HELLP syn-drome at any time postpartum in associationwith single- or multiple-organ injury (group2). In the absence of other disease conditions,

the 9 patients in group 1 responded rapidly to1 or 2 plasma exchange procedures with fewcomplications and no maternal deaths. In con-trast, in the 9 patients in group 2 with HELLPsyndrome presentations complicated by otherend-organ disease, the response to plasma ex-change was variable and there were 2 deaths inthis group. This series details the postpartumapplication of plasma exchange therapy forunremitting HELLP syndrome, but revealsthat a uniformly positive response to this ther-apy is not observed when there is additional

single or multiple organ injury.44 Potential ad-verse effects of this plasma exchange include

plasma-transmitted infections, anaphylaxis,volume overload, sepsis, and maternal death.

Maternal CounselingPregnancies complicated by HELLP syn-drome are associated with life-threateningcomplications for both the mother and her in-fant. Therefore, clinicians should be able toanswer questions regarding subsequent preg-nancy outcome and long-term prognosis.

Women with a history of HELLP syndromeare at increased risk of all forms of pre-eclampsia in subsequent pregnancies. In gen-eral, the rate of preeclampsia in subsequent

pregnancies is approximately 20% withsignificantly higher rates if the onset ofHELLP syndrome was in the second tri-mester. The rate of recurrent HELLP syn-drome ranges from 2% to 19%. We quotea recurrence risk of less than 5%.4547 Be-cause of these risks, these women areinformed that they are at increased riskfor adverse pregnancy outcome (pretermdelivery, fetal growth restriction, abruptio

placentae, and fetal death) in subsequentpregnancies. Therefore, they require closemonitoring during subsequent gestations.Currently, there is no preventive therapyfor recurrent HELLP syndrome. Liverfunction tests were studied in 54 womenat a median of 31 months (range, 3101months) after pregnancies complicated

by the HELLP syndrome.48 Serum levelsof AST, LDH, and conjugated bilirubin



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were found to be normal. Total bilirubinlevels, however, were elevated in 11(20%) of the studied women. The authorsof this report suggested the possibility thata dysfunction of the bilirubin-conjugatingmechanism represents a risk factor for thedevelopment of this syndrome.48

There are 2 reports describing long-term renal function after HELLP syn-drome.38,49 One of the reports included23 patients whose pregnancies were com-

plicated by HELLP syndrome and acute

renal failure; 8 of these women had 11 sub-sequent pregnancies with 9 resulting interm gestation.38 All 23 women also hadnormal blood pressures and renal functionat an average follow up of 4.6 years (range,0.511 years). The other study comparedrenal function after at least 5 years afterHELLP syndrome in 10 patients with therespective findings in 22 patients with pre-vious normotensive gestation.49 Therewere no differences in renal function tests

between the 2 groups. These findings sug-gest that the development of HELLP syn-

drome with or without renal failure doesnot affect long-term renal function.

SummarySignificant hepatic involvement by pre-eclampsia leading to hepatocyte necrosisand thrombocytopenia should alarm the cli-nician regardless of whether criteria forHELLP syndrome have been fully achieved.Liver parenchyma is relatively unforgivingof the endovascular insult presented by se-vere preeclampsia. This vasculopathy canresult in adverse maternal outcomes suchas DIC, subcapsular hematoma, hepatic in-farction, and death. The greatest challengesin caring for women with this disease are ap-

preciating the diagnosis, instituting timelyinterventions, and avoiding associated com-

plications. The addition of high-dose gluco-corticoids to the armamentarium of therapyfor HELLP syndrome may improve out-comes for both the mother and fetus, but de-finitive proof by randomized trials is lack-

ing. Delivery is the ultimate cure, and opti-mizing the status of a seriously ill patient

before delivery improves outcome.

References1. Levine RJ, Maynard SE, Qian C, et al. Circu-

lating angiogenic factors and the risk of pre-eclampsia. N Engl J Med. 2004;350:672683.

2. Pritchard JA, Weisman R, Ratnoff OD, et al.Intravascular hemolysis, thrombocytopeniaand other hemologic abnormalities associatedwith severe toxemia of pregnancy. N Engl JMed. 1954;250:8998.

3. Chesley LC. Disseminated intravascular co-agulation. In: Hypertensive Disorders inPregnancy. New York: Appleton-Century-Crofts; 1978:88118.

4. Weinstein L. Syndrome of hemolysis, elevat-ed liver enzymes, and low platelet count: asevere consequence of hypertension in preg-nancy. Am J Obstet Gynecol. 1982;142:159167.

5. Roberts JM, Cooper DW. Pathogenesis andgenetics of pre-eclampsia. Lancet. 2001;357:5356.

6. Roberts JM. Preeclampsia, what we knowand what we do not know. Semin Perinatol.2000;24:2428.

7. Barton JR, Riely CA, Adamel TA, et al. He- patic histopathologic condition does notcorrelate with laboratory abnormalities inHELLP syndrome (hemolysis, elevated liverenzymes, and low platelet count). Am J Ob- stet Gynecol. 1992;167:15381543.

8. Aarnoudse JG, Houthoff HF, Weits J, et al. Asyndrome of liver damage and intravascularcoagulation in the last trimester of normoten-sive pregnancy. A clinical and histopatholog-ical study. Br J Obstet Gynaecol. 1986;93:145155.

9. Arias F, Mancilla-Jimenez R. Hepatic fibrin-ogen deposits in pre-eclampsia. Immunoflu-orescent evidence. N Engl J Med. 1976;295:578582.

10. Barton JR, Sibai BM. Hepatic imaging inHELLP syndrome (hemolysis, elevated liverenzymes, and low platelet count). Am JObstet Gynecol. 1996;174:18201827.

11. Sibai BM, Taslimi MM, El-Nazer A, et al.Maternal-perinatal outcome associatedwith the syndrome of hemolysis, elevated



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liver enzymes, and low platelets in severepreeclampsia-eclampsia. Am J Obstet Gyne-col. 1986;155:501509.

12. Martin JN Jr, Rinehart B, May WL, et al. Thespectrum of severe preeclampsia:Comparativeanalysis by HELLP syndrome classification.Am J Obstet Gynecol. 1999;180:13731384.

13. VanPampus MG, Wolf H, Westenberg SM,et al. Maternal and perinatal outcome afterexpectant management of the HELLP syn-drome compared with preeclampsia withoutHELLP syndrome. Eur J Obstet GynecolReprod Biol. 1998;76:3136.

14. Visser W, Wallenburg HCS. Temporisingmanagement of severe pre-eclampsia withand without the HELLP syndrome. Br JObstet Gynaecol. 1995;102:111117.

15. Abramovici D, Friedman SA, Mercer BM,et al. Neonatal outcome in severe preeclamp-sia at 24 to 36 weeks gestation: does theHELLP (hemolysis, elevated liver enzymes,and low platelet count) syndrome matter?Am J Obstet Gynecol. 1999;180:221225.

16. Sibai BM. The HELLP syndrome (hemoly-sis, elevated liver enzymes, and low plate-lets): much ado about nothing? Am J ObstetGynecol. 1990;162:311316.

17. Weinstein L. Preeclampsia/eclampsia withhemolysis, elevated liver enzymes andthrombocytopenia. Obstet Gynecol. 1985;66:657660.

18. Sibai BM, Ramadan MK, Usta I, et al.Maternal morbidity and mortality in 442pregnancies with hemolysis, elevated liverenzymes, and low platelets (HELLP syn-drome). Am J Obstet Gynecol. 1993;169:10001006.

19. Sibai BM. Diagnosis and management ofgestational hypertension and preeclampsia.Obstet Gynecol. 2003;102:181192.

20. Clark SL, Phelan JR, Allen SH, et al. Ante-partum reversal of hematologic abnormali-ties associated with the HELLP syndrome.J Reprod Med. 1987;32:781784.

21. Magann EF, Bass D, Chauhan SP, et al. An-tepartum corticosteroids: disease stabiliza-tion in patients with the syndrome ofhemolysis, elevated liver enzymes, and lowplatelets (HELLP). Am J Obstet Gynecol.1994;171:11481153.

22. Magann EF, Perry KG Jr, Meydrech EF, et al.Postpartum corticosteroids: acceleratedrecovery from the syndrome of hemolysis,

elevated liver enzymes, and low platelets(HELLP). Am J Obstet Gynecol. 1994;171:11541158.

23. Tompkins MJ, Thiagarajah S. HELLP (he-molysis, elevated liver enzymes, and lowplatelet count) syndrome: the benefit of cor-ticosteroids. Am J Obstet Gynecol. 1999;181:304309.

24. OBrien JM, Milligan DA, Barton JR. Im- pact of high-dose corticosteroid therapy forpatients with HELLP (hemolysis, elevatedliver enzymes, and low platelet count) syn-drome. Am J Obstet Gynecol. 2000;183:

921924.25. Vigil-DeGracia P, Garcia-Caceres E. Dexa-

methasone in the postpartum treatment ofHELLP syndrome. Int J Gynaecol Obstet.1997;59:217221.

26. Yalcin OT, Sener T, Hassa H, et al. Effects ofpostpartum corticosteroids in patients withHELLP syndrome. Int J Gynaecol Obstet.1998;61:141148.

27. Isler CM, Barrilleaux PS, Magann EF, et al.A prospective, randomized trial comparingthe efficacy of dexamethasone and betame-thasone for the treatment of antepartumHELLP syndrome. Am J Obstet Gynecol.

2001;184:13321339.28. Sibai BM. Diagnosis, controversies, and

management of the syndrome of hemolysis,elevated liver enzymes, and low plateletcount. Obstet Gynecol. 2004;103:981991.

29. OBrien JM, Shumate SA, Satchwell SL,et al. Maternal benefit to corticosteroidtherapy in patients with HELLP (hemolysis,elevated liver enzymes, and low platelets)syndrome: impact on the rate of regional an-esthesia. Am J Obstet Gynecol. 2002;186:475479.

30. Martin JN Jr, Thigpen BD, Rose CH, et al.Maternal benefit of high-dose intravenouscorticosteroid therapy for HELLP syn-drome. Am J Obstet Gynecol. 2003;189:830834.

31. Bush K, OBrien JM, Milligan DA, et al. Theutility of umbilical artery Doppler in womenwith the HELLP (hemolysis, elevated liverenzymes, and low platelets) syndrome. AmJ Obstet Gynecol. 2001;184:10871089.

32. Briggs R, Chari RS, Mercer B, et al. Post-operative incision complications aftercesarean section in patients with antepar-tum syndrome of hemolysis, elevated liver



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enzymes, and low platelets (HELLP): doesdelayedprimary closuremake a difference?Am J Obstet Gynecol. 1996;175:893896.

33. Chelmow D, Rodriguez EJ, Sabatini MM.Suture closure of subcutaneous fat andwound disruption after cesarean delivery:a meta-analysis. Obstet Gynecol. 2004;103:974980.

34. Goodlin RC, Anderson JC, Hodgson PE.Conservative treatment of liver hematomain the postpartum period. J Reprod Med.1985;30:368370.

35. Manas KJ, Welsh JD, Rankin RA, et al.

Hepatic hemorrhage without rupture inpreeclampsia. N Engl J Med. 1985;312:424426.

36. Neerhof MG, Zelman W, Sullivan T. Hepaticrupture in pregnancy: a review. Obstet Gyne-col Surv. 1989;44:407409.

37. Sibai BM, Mabie BC, Harvey CJ. Pulmonaryedema in severe preeclampsia-eclampsia:analysis of 37 consecutive cases. Am J ObstetGynecol. 1987;156:11741179.

38. Sibai BM, Ramadan MK. Acute renal failurein pregnancies complicated by hemolysis,elevated liver enzymes, and low platelets.AmJ Obstet Gynecol. 1993;168:16821687.

39. Smith LG Jr, Moise KJ Jr, Dildy GA, et al.Spontaneous rupture of the liver during preg-nancy: current therapy. Obstet Gynecol.1991;77:171175.

40. Loevinger EH, Lee WM, Anderson MC.Hepatic rupture associated with preg-nancy: treatment with transcatheterembolotherapy. Obstet Gynecol. 1985;65:281284.

41. Martin JN Jr, Perry KG, Blake PG, et al.Better maternal outcomes are achievedwith dexamethasone therapy for postpartumHELLP (hemolysis, elevated liver enzymes,

and thrombocytopenia) syndrome. Am J

Obstet Gynecol. 1997;177:10111017.42. Martin JN Jr, Files JC, Blake PG, et al.

Plasma exchange for preeclampsia: I. Post- partum use for persistently severe pre-

eclampsia-eclampsia with HELLP syndrome.Am J Obstet Gynecol. 1990;162:126137.

43. Martin JN Jr, Files JC, Blake PG, et al. Post-

partum plasma exchange for atypical pre-eclampsia-eclampsia as HELLP syndrome.Am J Obstet Gynecol. 1995;172:11071127.

44. Schwartz ML. Possible role for exchange plasmapheresis with fresh frozen plasma

for maternal indications in selected casesof preeclampsia and eclampsia. ObstetGynecol. 1986;68:136139.

45. Sibai BM, Ramadan MK, Chari RS, et al.Pregnancies complicated by HELLP syn-drome (hemolysis, elevated liver enzymes,

and low platelets): Subsequent pregnancy

outcome and long-term prognosis. Am JObstet Gynecol. 1995;172:125129.

46. Van Pampus MG, Wolf H, Mayruhu G, et al.Long-term follow-up in patients with a histo-

ry of (H)ELLP syndrome. Hypertens Preg-nancy. 2001;20:1523.

47. Chames MC, Haddad B, Barton JR, et al.Subsequent pregnancy outcome in women

with a history of HELLP syndrome at#28weeks of gestation. Am J Obstet Gynecol.

2003;188:15041508.48. Knapen M, VanAltena A, Peters WHM, et

al. Liver function following pregnancycomplicated by the HELLP syndrome. Br

J Obstet Gynaecol. 1998;105:12081210.49. Jacquemyn Y, Jochems L, Duiker E, et al.

Long-term renal function after HELLP

syndrome. Gynecol Obstet Invest. 2004;57:117120.


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